Ultrasonic method and device for wound treatment

ABSTRACT

An apparatus and method are provided for applying a medicament to tissue, and delivering ultrasonic energy from a non-contact distance from the tissue to the medicament and to the tissue, wherein the ultrasonic energy has intensity capable of penetrating the wound tissue to a beneficial depth to provide a therapeutic effect to the tissue, and of sonicating the medicament for causing the medicament to penetrate the tissue to a beneficial depth to provide a therapeutic effect to the tissue.

RELATED APPLICATION

This application is a continuation of application Ser. No. 10/815,384filed Apr. 1, 2004, which in turn is a continuation-in-part ofapplication Ser. No. 10/409,272 filed Apr. 7, 2003, which in turn is acontinuation-in-part of application Ser. No. 09/669,312, filed Sep. 25,2000, now U.S. Pat. No. 6,569,099, issued May 27, 2003, each of which ishereby fully incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to methods of using ultrasonic waves inwound treatment. More particularly, the present invention relates to amethod of applying a medicament to tissue and delivering ultrasoundenergy to the medicament and the tissue.

BACKGROUND

Ultrasonic waves have been widely used in medical applications,including for both diagnostics and therapy as well as for manyindustrial applications. One diagnostic use of ultrasound waves includesusing ultrasonic waves to detect underlying structures in an object or ahuman tissue. In this procedure, an ultrasonic transducer is placed incontact with the object or tissue via a coupling medium, and highfrequency (1-10 MHz) ultrasonic waves are directed into the tissue. Uponcontact with various underlying structures, the waves are reflected backto a receiver adjacent the transducer. By comparison of the signals ofthe ultrasonic wave as sent with the reflected ultrasonic wave asreceived, an image of the underlying structure can be produced. Thistechnique is particularly useful for identifying boundaries betweencomponents of tissue and can be used to detect irregular masses, tumors,and the like.

Two therapeutic medical uses of ultrasound waves include aerosol mistproduction and contact physiotherapy. Aerosol mist production makes useof a nebulizer or inhaler to produce an aerosol mist for creating ahumid environment and delivering drugs to the lungs. Ultrasonicnebulizers operate by the passage of ultrasound waves of sufficientintensity through a liquid, the waves being directed at an air-liquidinterface of the liquid at a point underneath or within the liquid.Liquid particles are ejected from the surface of the liquid into thesurrounding air following the disintegration of capillary waves producedby the ultrasound energy. This technique can produce a very fine densefog or mist. Aerosol mists produced by ultrasound are preferred overaerosol mists produced by other methods because a smaller particle sizeof aerosol can be obtained with the ultrasonic waves. One of the majorshortcoming of inhalers and nebulizers is that the aerosol mist cannotbe directed to a target area without an air stream, which decreases theefficiency of the ultrasound energy. Ultrasonic sprayers such as thosesold by Sonic and Materials Inc., Misonix Inc., Sono-Tek Inc. (see, forexample, U.S. Pat. Nos. 4,153,201, 4,655,393, and 5,516,043) operate bypassing liquid through a central orifice of an ultrasoundinstrument-tip. Major disadvantages of these sprayers includenon-uniform particle size, heating of liquid flow, and less efficiencyof ultrasound waves because of a demolished end (radiation) surfaceconfiguration of the tip.

Contact physiotherapy applies ultrasonic waves directly to tissue in anattempt to produce a physical change in the tissue. In conventionalultrasound physiotherapy, an ultrasonic wave contacts the tissue via acoupling medium. Ultrasonic waves produced by the transducer travelthrough the coupling medium and into the tissue. The coupling medium istypically a bath of liquid, a jelly applied to the surface to betreated, or a water-filled balloon. Conventional techniques provideultrasonic waves having an intensity of about 0.1 w/cm² to 3 w/cm² at afrequency of about 0.8 to 3 Megahertz. The treatment is applied to askin surface for from about 1 to 30 minutes, two or three times a week.The coupling medium can provide a cooling effect which dissipates someof the energy produced by the ultrasonic transducer.

More importantly, a coupling medium or direct contact between the tissueand ultrasonic transducer is necessary to transmit the ultrasonic wavesto the skin surface because ambient air is a relatively poor medium forthe propagation of ultrasonic waves.

Several beneficial effects have been reported from contact ultrasoundphysiotherapy, such as, for example, the following: local improvement ofthe blood circulation, heating of the tissue, accelerated enzymeactivity, muscle relaxation, pain reduction, and enhancement of naturalhealing processes. Despite these beneficial effects, current techniquesof medical physiotherapy using ultrasonic waves are limited by thenecessity of providing a direct contact interface between the ultrasonictransducer and the tissue to maintain an effective transmission of theultrasonic waves from the transducer to the tissue.

The necessity of direct contact with or without a coupling medium makescurrent methods undesirable. Some tissue conditions may be accessible tocontact ultrasound devices but would be impractical for contactultrasound treatment. For example, fresh or open wounds resulting fromtrauma, burns or surgical interventions are not suitable for directcontact ultrasound treatment because of the structural nature of theopen wound and the painful condition associated with those wounds.Moreover, conventional contact ultrasound may have a destructive effecton these types of open wounds due to the close proximity of anoscillating tip of an ultrasonic transducer relative to the alreadydamaged tissue surface.

SUMMARY

The present invention provides an apparatus and a method for treatingtissue, the apparatus including a generator and a transducer forgenerating ultrasonic energy and delivering the ultrasonic energy to thebiological tissue, from a non-contact distance from the tissue, whereinthe generated ultrasonic energy has an intensity capable of penetratingthe wound tissue to a beneficial depth to provide a therapeutic effectto the tissue, and of sonicating the medicament for causing themedicament to penetrate the tissue to a beneficial depth to provide atherapeutic effect to the tissue.

The present invention further provides an apparatus and method forgenerating ultrasonic energy from a non-contact distance from thesurface of the wound; and delivering the generated ultrasonic energy tothe wound through a gaseous medium (“dry” approach), wherein thegenerated ultrasonic energy has an intensity capable of penetrating thewound tissue to a beneficial depth to provide a therapeutic effect fordecreasing the healing time for the wound.

The present invention further relates to a method and device forspraying (“wet” approach) a wound surface to deliver drugs, killbacteria, or cleanse a surface by non-contact application of anultrasound transducer tip. The method applies ultrasonic waves to thewound without requiring direct or indirect (via a traditional couplingmedium) contact between the ultrasonic wave transducer and the wound tobe sprayed.

The method of the invention comprises producing a directed spray ofliquid or powder particles produced by contact of the liquid or powderwith a free end surface of an ultrasonic transducer. The ultrasonicwaves cause the spray to project outwardly from the distal end surfaceof the ultrasonic transducer, and the particle spray is directed ontothe wound. The particles of the spray provide a medium for propagationof the ultrasonic waves emanating from the distal end surface. Accordingto the method of the present invention a directed particle spray createdby low frequency ultrasound waves onto a wound, delivers drug, killsbacteria on the wound, increases blood flow, and removes dirt and othercontaminants from the wound's surface (mechanical cleansing).

This method of drug delivery is particularly advantageous on tissues forwhich local topical application of a drug is desirable but contact withthe tissue is to be avoided. Furthermore, the low frequency ultrasoundwaves used in the method energize the drug and cause penetration of thedrug below the surface of the tissue, due to acoustic pressure,microcavitation, etc. Finally, the bacteria killing method is effectivewhen applied to the surface whether the liquid or powder sprayed is adrug (an antiseptic or antibiotic), oil, saline, distilled water, etc.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an ultrasonic wound treatment systemaccording to the present invention.

FIG. 2 is a lateral schematic view of an ultrasonic sprayer according tothe present invention.

FIG. 3 is a partly cross-sectional view of an ultrasonic sprayeraccording to the present invention.

FIG. 4 a is a detailed view of the sprayer illustrated in FIG. 3 forspraying liquid from a radiation surface.

FIG. 4 b is a detailed view of the sprayer illustrated in FIG. 3 forspraying liquid from a side (radial) surface.

FIG. 5 is a cross-sectional front view of a distal end of an ultrasonictransducer when liquid is delivered to the side or radiation surface ofthe transducer tip from 360° along its perimeter.

FIG. 6 is a variation of FIG. 4 b illustrating the spraying effect bychanging the angle between the ultrasound instrument and horizontal linefrom 0° to 90°.

FIGS. 7 a-7 g are each a front cross-sectional view of an ultrasound tipconfiguration.

FIGS. 8 a-8 i are each an enlarged side view of a different modificationof a tip end shape of the ultrasonic sprayer according to the presentinvention.

FIGS. 9 a, 9 b, and 9 c represent cross-sectional, distal, and lateralviews, respectively, of the top of an ultrasonic sprayer having a slot,groove, or thread.

FIG. 10 is a schematic representation of a method of delivery ofultrasonic energy delivered through a gaseous medium, accordance withanother embodiment of the present invention.

FIG. 11 is a plot of experimental results achieved upon deliveringultrasound energy substantially through a gaseous medium to a wound inaccordance with the present invention.

DETAILED DESCRIPTION

The device of the invention that produces a spray is characterized bymeans for first delivering the liquid to a lateral surface of anultrasonic transducer tip adjacent to a free end surface such that theliquid is pulled to the free end surface by a vacuum (negative pressure)created by the ultrasound waves on the free end surface of thetransducer tip. This effect can be achieved while the angle between theultrasound instrument and the horizontal is modified up to 90°. (Thisacoustical effect of delivering liquid from radial side of a tip to thefree end was discovered by the inventor of this invention and is calledthe “Babaev effect”.) This effect occurs when liquid is delivered to theradial surface of a transducer tip about its perimeter, up to 360° aboutits perimeter, e.g. from the top, side, bottom, etc.

For the above purpose the device can have a so-called nozzle constructedfrom steel (non-disposable) or plastic (disposable) with a suitablevalve design. The nozzle allows delivery of liquid to the lateralsurface of the transducer tip or directly to the distal side (radiationsurface) of the ultrasound transducer, for enabling the transducer toact as a sprayer or atomizer.

One of the major advantages of the invention is the uniformity of thespray particles generated. Because liquid or powder is sprayed from asolid radiation surface, there is substantial uniformity of particlesize, about 90% or greater, such as from about 90 to 96%. It is providedthat the distal radiation surface is driven with constant frequency andamplitude to create the spray. It is also provided that the frequencyand/or amplitude can be modulated during treatment and that the distalradiation surface is driven with a sinusoidal, rectangular, trapezoidalor triangular wave form.

The step of producing the spray can further include operating thetransducer to produce ultrasonic waves having a frequency of from about18 kHz to 10,000 MHz. Frequencies below 18 kHz, i.e., from about 1 to 18kHz, can be used as well; however, this lower range is less desirablebecause this range of sound wave can be uncomfortable to the patient andoperator (without ear protection or the like). Frequencies in the rangeof from about 30 to 100 kHz are used in some embodiments, andfrequencies of about 40 kHz are used in one embodiment.

The separation distance between the free end surface of the transducerand the surface or object to be sprayed should be a “non-contact”distance of at least 0.1 in. (2.5 mm). In one embodiment, the separationdistance is from about 0.1 in. (2.5 mm) to 20 in. (51 cm), for examplefrom about 0.1 in. (2.5 mm) to 5 in. (12.7 cm). The liquid or powder tobe sprayed can be any appropriate carrier such as water (regular ordistilled), saline solution, or oil to be applied to tissue (i.e.,biological tissue or non-biological tissue), such as a vegetable,peanut, or canola oil, optionally with a soluble pharmaceutical, e.g.,an antibiotic, antiseptic, conditioner, surfactant, emollient, or otheractive ingredient. The pharmaceutical or the like can be present in aconcentration sufficiently low to be soluble but high enough to beeffective for the intended purpose.

It is within the scope of the invention that the liquid to be sprayedcould include a mixture of two or more immiscible liquids or aheterogeneous mixture of a solution and small particles. It is alsowithin the scope of the invention that the spray could includeparticles, such as powder, and that the liquid in the reservoir couldinclude powder.

The spray produced according to the invention is directed to the object,surface, or tissue to be sprayed for the time and frequency required foraccomplishing a particular purpose or treatment. It is believed that aminimum length of spray of at least one second will be required;however, the length or duration of the spray could be from about onesecond to as much as a minute or more, even 30 minutes. Numerous factorsor circumstances, such as, for example, the area to be sprayed (e.g.,the size of a wound), the volume rate of spray produced, theconcentration of active ingredient, etc., will impact upon the durationand/or frequency of the spraying. Spraying could be required from one ormore times daily to as little as two or three times a week or month.

According to embodiments, ultrasonic waves are applied to a woundwithout establishing contact, directly or indirectly, between theultrasonic transducer and the wound. For example, surfaces of the humanbody especially suited for treatment in accordance with the method ofthe present invention include infected and inflammatory situations inopen wounds, including trauma or gun shut wounds, fire and chemicalburns.

In addition, embodiments of the method can be suited to directing aspray into orifices or other body crevices that are difficult to access.

Wound treatment according to the method and apparatus of the presentinvention has several advantages. First, this method topically appliesmedicines such as liquid antibiotics to the wound surface without theneed to contact infected, inflamed or painful tissue with an instrument.And second, a significant bactericidal effect occurs when a woundsurface is sprayed using the method of the present invention.

Moreover, aside from the bactericidal effect and advantages ofnon-contact treatment, it has been found that using the method of thepresent invention gave a significant reduction in volume used of liquidmedicine used as compared with traditional methods for wound treatment.Similarly, this allows for precise dosage of the sprayed liquid topermit a user, such as a physician, to administer the desired volume ofliquid at a desired rate and duration.

It has been found that the method of the present invention decreaseshealing times for inflammatory and purulent infected wounds from about1.5 to 3 times faster than traditional methods. This effect results froma bactericidal, blood flow increasing and mechanical cleansing effect ofthe atomized spray particles, which have ultrasound energy due to theultrasonic waves. The spray mechanically scrubs the surface of tissue toremove dirt, dead tissue, and purulent buildup on the tissue surface.The mentioned healing effect also results of energized and highlyactivated antibiotics, and drug penetration into the tissue surface upto 0.5 mm in depth under influence of ultrasound waves.

Additionally, a combination of the low frequency ultrasonic waves andthe sonicated medicines (highly activated by ultrasonic energy) destroysthe surface bacteria, resulting in a higher disinfecting property ofsonicated liquids as compared to ordinarily applied liquids.

The spray of the present method also stimulates healthy cell growth toaid in granulation and epithelization of the healing tissue.

Other applications of the invention can be directed to non-medical usessuch as cleansing, sterilizing and coating surfaces of objects and food.

The method of the present invention offers an approach that mayre-establish use of some traditional antibiotics and establish a methodfor fighting bacteria without antibiotics when necessary. The effect ofthe method of the present invention in highly activating antibiotics mayallow some traditional antibiotics to overcome bacteria which havebecome resistant to that antibiotic. Moreover, independent of thesonication effect of the antibiotics, the low frequency ultrasonic wavesapplied in accordance with the method of the present inventionphysically destroy bacteria. The combination of the highly activatedantibiotics and of the low frequency ultrasonic waves in accordance withthe method of the present invention produce a strong bactericidal effectnot found in mere topical application or oral ingestion of antibiotics.This combined effect has been shown to significantly increase thehealing of purulent infected wounds.

The present method also provides a system of non-contact drug deliverywithout use of a compression sprayer system. This simplifies the designof a non-contact drug delivery sprayer and reduces the weight of thesprayer. More importantly, not using compression to propel the atomizedparticles preserves the ultrasound energy carried by the sprayparticles.

Delivery of ultrasound energy in accordance with the present inventionhas been proven to destroy bacteria by action of the ultrasonic wavesand by highly activated liquid medicines applied to the tissue.

The method of the present invention provides a method of compressionlessnon-contact drug delivery.

The invention is better appreciated by making reference to the drawings.In FIG. 1, an ultrasonic treatment system 2 includes an ultrasoundgenerator 4, connected to an ultrasound transducer 6 by a cable 8. Thegenerator 4, which is conventional, may have a front panel 10 with apower button 12, a timer 14, a control button 16, a display 18, and oneor more jacks 20, for example, for connecting a footswitch. A nozzle 22having a liquid reservoir 24 with a valve 26 is attached to the distalportion of transducer 6. Arrows 28 represent the direction of the sprayproduced.

FIG. 2 is a simplified representation of an ultrasonic device and sprayaccording to the invention. Transducer 6 has a distal transducer tip orhorn 30. Liquid from a liquid reservoir 32 flows through a valve 34 to aposition adjacent the distal radiation surface 36 of a horn 30.Transducer 6 is attached to an ultrasound source via cable 8. A liquidmist is directed in the direction of arrows 38 to target tissue orsurface 40 (wet approach).

FIG. 3 is an enlarged, partly cross-sectional view of a section of FIG.1 illustrating a spray created by the device according to the method ofthe present invention. This device is a modification and implementationof a device disclosed in U.S. Pat. No. 5,076,266, which is incorporatedherein by reference. As can be seen in more detail in FIG. 3, nozzle 22surrounds ultrasound horn 30. Also, liquid reservoir 32 has a valve 34positioned between reservoir 32 and the distal surface 36 of ultrasonichorn 30. A conical spray pattern of liquid particles 42 is directed at asurface or tissue 44 of a target. This configuration is effective tospray liquid onto a surface and to deliver ultrasonic waves to thatsurface, such as, for example, the surface of a wound.

Valve 34 allows liquid to flow to distal tip 36 as drops or as acontinuous flow through gap 46. Valve 34 may be located anywhere,including between reservoir 32 and horn 30. Mechanical movement of thehorn 30 in the direction x-x causes liquid to flow to the distal end ofradiation surface 36.

FIG. 4( a) is a view of the ultrasonic sprayer as used in accordancewith the method of the present invention for spraying liquid 48 directedto distal end (radiation surface) 36.

FIG. 4( b) is a view of the basic spraying method from side (radial)surface of the tip based on the Babaev effect. In this example, liquidor drug directed to the radiation surface 36 of ultrasound horn 30becomes sonicated (ultrasonically energized), after being pulled forwardby negative pressure (vacuum) created by ultrasound waves and sprays.

As shown in FIG. 5, liquid is delivered to the side of radiation surface36 of transducer horn 30 about the perimeter of radiation surface 36, upto 360° about its perimeter, e.g. from the top, side, bottom, etc.

In the embodiment of the invention shown in FIG. 6, a partial section oftransducer horn 30 is elevated from the horizontal up to 90°. Due to theBabaev effect, liquid 48 still travels to radiation surface 36.

The ultrasound tip or horn may have a regular or irregular lateralcross-section, including circular, oval, elliptical, rectangular,trapezoidal, or a combination thereof. For example, FIGS. 7( a) to 7(g)are each a view of a cross-section of an ultrasound tip or horn. Also,the distal end shape of the ultrasound tip or horn longitudinalcross-section may vary, and may be rectangular, elliptical, oval,spherical, conical, curved, stepped, with chamfer, etc., as shown inFIGS. 8( a) to 8(n), which are each an enlarged view in section of adifferent, exemplary modification of a tip of the sprayer as used inaccordance with the method of the present invention. The shape can berectangular in one embodiment, because radiation beams from ultrasoundtip surface are substantially fully directed to the target (wound). Withthe spherical, elliptic and oval (FIG. 8( e)) form or shape of thedistal end, radiation beams are focused at a focal point. However, withother forms or shapes of the distal end, radiation beams are spread,thus partially reaching the target.

Radial side surface of the distal end of the tip may have a slot(groove) or thread for liquid to be directed to the radiation surface(FIGS. 9 a-9 c).

FIGS. 9 a to 9 c are each a view of a radial side surface of the distalend of the tip which has a slot (groove) 19 or thread 20 for liquid tobe directed to the radiation surface.

The ultrasonic energy delivered has an intensity capable of providing atherapeutic effect to the wound 40, exerting acoustic pressure and/orcausing micro-cavitation. Acoustic pressure refers to a force that canbe felt which is exerted through air between the transducer and thetissue being targeted. Microcavitation refers to the formation andpulsation of gas or vapor filled microscopic bubbles in fluids as aresult of ultrasonically induced and regularly repeated pressurechanges. Advantages to micro cavitation include the creation of acousticstreaming which is a steady circulation of fluid in blood vesselsinduced by ultrasound radiation force.

In one embodiment, the amplitude achieved by the ultrasonic energy is atleast 3 microns, and at least 10 microns in one embodiment. Inembodiments, the frequency used is in the range of 20 kHz-50 MHz,wherein a range is 20-200 kHz in some embodiments, another range is20-40 kHz in embodiments and a value is 40 kHz in embodiment, whereinthe lower limit of the frequency used is outside of the human hearingrange in embodiments.

Furthermore, it is advantageous in embodiments to use a radiationsurface 36 having a shape and size selected to achieve delivery of theultrasonic energy to the wound where the delivered ultrasonic energy hasan intensity capable of providing a therapeutic effect to the wound.Selection of the shape and size of the radiation surface 36 incombination with selection of the frequency and amplitude of theultrasonic energy used is advantageous in achieving delivery of theultrasonic energy to the wound wherein the ultrasonic energy has anintensity capable of achieving a therapeutic effect to the wound. Inembodiments, the radiation surface 36 has a relatively large diameter.Actual selection of the diameter is dependent upon the frequency andamplitude selected. Furthermore, the shape of the radiation surface 36is selected from one of flat, concave, convex, or a combination thereof,and from the configurations shown in FIGS. 8 a-8 i, or a combinationthereof.

In another embodiment, ultrasonic energy is delivered to the woundwithout the use of the spray, i.e., the ultrasonic energy is deliveredthrough a medium other than a spray, including a gaseous medium, such aspure air, e.g., ambient air, where the ultrasound transducer 6 ispositioned at a non-contact distance from the wound for providing atherapeutic and beneficial effect. The ultrasound waves, even withoutthe use of a spray, destroy surface bacteria and stimulate health cellgrowth. This method of wound treatment is particularly advantageous onwounds for which contact with the wound should be avoided.

With reference to FIG. 10, an ultrasonic treatment system 2′ is shownincluding an ultrasound generator 4′ connected to an ultrasoundtransducer 6′ by a cable 8′ for generating ultrasound energy. Transducer6′ has a radiation surface 36′ from which the ultrasound energy isemitted and directed to wound 40′. The generator 4′, which isconventional, may have a front panel 10′ with a power button 12′, atimer 14′, a control button 16′, a display 18′, and one or more jacks20′, for example, for connecting a footswitch. Arrows 100 represents thedirection of ultrasound energy generated and directed toward wound 40′.Unlike the above embodiments, a liquid or powder is not contacted withthe ultrasonic transducer for generating a spray and directing it to thewound 40′. The ultrasonic energy is delivered through a medium otherthan a spray, including a gaseous medium, such as pure air (“dry”approach). A horn of the transducer 6′ may be configured in accordancewith the embodiments shown in FIGS. 7 a-g, 8 a-i and/or 9 a-c.

In one embodiment, wherein the ultrasonic energy is delivered to thewound 40′ through a gaseous medium, such as pure air, for achieving atherapeutic effect at the wound 40′, the frequency of the ultrasonicenergy generated is selected to be a low frequency. By using a lowfrequency, a particular or predetermined amplitude for the generatedultrasonic energy is achieved, which is capable of being delivered tothe wound with an intensity capable of providing a therapeutic effect tothe wound 40′, exerting acoustic pressure and/or causingmicro-cavitation. In embodiments, the amplitude achieved by theultrasonic energy is at least 3 microns, such as at least 10 microns. Inembodiments, the frequency used is in the range of 20 kHz-50 MHz,wherein a range is 20-200 kHz in embodiments, 20-40 kHz in otherembodiments, and a is 40 kHz in one embodiment, wherein the lower limitof the frequency used is outside of the human hearing range inembodiments.

Furthermore, it is advantageous to use a radiation surface 36′ having ashape and size selected to achieve delivery of the ultrasonic energy tothe wound where the delivered ultrasonic energy has an intensity capableof providing a therapeutic effect to the wound. Selection of the shapeand size of the radiation surface 36′ in combination with selection ofthe frequency and amplitude of the ultrasonic energy used isadvantageous in achieving delivery of the ultrasonic energy to the woundwherein the ultrasonic energy has an intensity capable of achieving atherapeutic effect to the wound. In embodiments, the perimeter of theradiation surface 36′ is round, rectangular, elliptical, oval,spherical, conical, curved, stepped, with chamfer, etc., or acombination thereof, as shown in FIGS. 8( a) to 8(n), and has arelatively large diameter. Actual selection of the diameter is dependentupon the frequency and amplitude selected. Furthermore, the shape of theradiation surface 36′ is selected from one of flat, concave, convex, anda combination thereof.

With respect to FIG. 11, results are shown of experimentation atCelleration Acoustic Laboratory, Eden Prairie, Minn. Ultrasonic energyhaving an intensity capable of providing a therapeutic effect wasdelivered through air (no spraying of liquid or powder) to a wound usingan ultrasound transducer positioned at a non-contact distance from thesurface of the wound, as shown by FIG. 10. The ultrasonic energy wasgenerated at a frequency of 40 kHz and an amplitude of 61 microns. Thetransducer radiation surface was flat, rounded and had a diameter of 1cm. Hydrophone model number PVDF-Z44-1000 and hydrophone amplifier modelnumber Al7db, both manufactured by ONDA Corporation, Sunnyvale, Calif.,were employed, using an amplifier gain of 7.44. As shown, with thetransducer positioned at a distance of between 2.5 mm and 38 mm from awound, ultrasonic energy was delivered to the wound having an intensitycapable of providing a therapeutic effect to the wound; the intensitybeing within the range of from 0.1 W/cm² to 10 W/cm².

With respect to FIGS. 10-11, the ultrasound energy is delivered to thewound or tissue being treated through a medium other than a spray,including a gaseous medium, such as pure air, e.g., ambient air,including without the use of the spray. Accordingly, the ultrasoundenergy is delivered to the tissue through a substantial expanse of asubstantially purely gaseous medium, such as ambient air. Inembodiments, the transducer can be positioned at a non-contact distancefrom the tissue, where the space between the transducer and the tissuethrough which the ultrasound energy is delivered is an expanse of asubstantially purely gaseous medium spanning a distance of at leastabout 0.1 in. (2.5 mm) from the transducer to the tissue. Inembodiments, the distance spanned is from about 0.1 in. (2.5 mm) to 20in. (51 cm), and is from about 0.1 in. (2.5 mm) to 5 in. (12.7 cm) insome embodiments.

The embodiment shown in FIGS. 2-6 may further be used for deliveringultrasound energy to the skin without the use of a spray by notproviding a liquid within the reservoir 32 so that liquid does not flowto the radiation surface 36, or by selectively controlling delivery ofliquid from the reservoir to the radiation surface 36 in accordance withone or more requests from an operator and/or a control module. Theoperator may make a request via a selection device which may bemechanical and/or electrical, e.g., a button, trigger, lever and/or userinterface. The request may be processed mechanically and/or electrically(by analog and/or digital processing) for mechanically controlling flowof the liquid, such as by controlling the valve 34 to remain open orclosed or sequentially open and close, in any order. Accordingly,non-contact ultrasound treatment without a spray may be provided totissue using either the embodiment shown in FIGS. 1-6 or the embodimentshown in FIG. 10.

As described further below, the reservoir may be provided in a deviceseparate from the transducer and the spray may be generated anddelivered from another device separate from the transducer, where theseparate device may be detached from or attached to the transducer. Thespray from the separate device may be a spray generated and delivered byanother transducer or by a device that does not use ultrasound energy.Similar to the embodiment described with respect to FIGS. 1-6 in whichthe spray is delivered simultaneously with delivery of the ultrasoundenergy, the spray delivered from a separate device may be deliveredsimultaneously with delivery of the ultrasound energy. Alternatively,the spray may be delivered prior to delivery of the ultrasound energy,as described further below. Furthermore, a treatment may include aseries of continual and/or intermittent treatments, wherein individualtreatments of the series of treatments are selected from the groupconsisting of: delivery of ultrasound energy with the use of a spray,i.e., the wet approach as described with respect to FIGS. 1-6; anddelivery of ultrasound energy through a medium other than a spray (i.e.,a gaseous medium), i.e., the dry approach as described with respect toFIG. 10, with the two or more steps performed in any order. Accordingly,non-contact ultrasound treatment with or without a spray may be providedto tissue using either using the embodiment described with respect toFIGS. 1-6 or the embodiment shown in FIG. 10.

The liquid or powder to be sprayed (via the reservoir 32, valve 34 andradiation surface 36 shown in FIGS. 1-6 or via a separate device) may bean analgesic, such as for use as a local anesthetic, such as prior to adental procedure, suturing, or other invasive or noninvasive procedureor for relief of pain. The analgesic is sonicated, providing a moreimmediate effect, a more potent effect, further penetration into theskin, improved precision of dosage, and a more targeted affect forminimizing effects to untargeted tissue. Moreover, independent of theeffect of the sonicated analgesic, the low frequency ultrasonic wavesapplied in accordance with a method of the present invention, such asthrough the medium of a spray formed from a saline solution, provide ananalgesic effect. The combination of the sonicated analgesic and of thelow frequency ultrasonic waves in accordance with a method of thepresent invention produce a strong local anesthetic effect not found inmere topical application of analgesics.

Another embodiment of a method of the invention includes the step ofproviding a substance, such as a medicament and herein referred to asmedicament, for application of the medicament to tissue, and deliveringultrasound energy to the medicament as it is applied or once it isapplied and to the tissue using the embodiment shown in FIGS. 1-6 or theembodiment shown in FIG. 10, and the amplitude, frequency, non-contactdistance and other parameters for the ultrasound energy, generator andtransducer described above. The ultrasound energy is delivered by anon-contact delivery (i.e., without contacting the transducer 6 or 6′ tothe tissue) to the tissue, as described above, and may be deliveredthrough a spray or without a spray, e.g., by delivering the ultrasoundenergy through a medium other than a spray, such as ambient air, gas,etc. The medicament is, for example, an antibiotic, an ointment, cream,gel, liquid, salve, oil, saline solution, distilled, non-distilledand/or boiled water, powder, spray, antibacterial agent, antisepticagent, insulin, analgesic agent, conditioner, surfactant, emollient, orother active ingredient, or a combination thereof.

The medicament may be applied directly to the tissue before theultrasound energy is delivered to the tissue, and/or during the deliveryof the ultrasound energy to the tissue. The medicament may be providedwithin at least one container from which the medicament is applied tothe tissue, where the container is in contact with the tissue, proximatethe tissue and/or spaced from the tissue and oriented for directing themedicament at the tissue. The container may have a permeable wall(s)through which the medicament may pass directly to or towards the tissue,manually, automatically and/or mechanically, and/or through which theultrasound energy may penetrate. The container may be integrated with orseparated from the housing of the transducer 6 or 6′. Furthermore, themedicament may be applied below the tissue in addition to or instead ofto the surface of the tissue.

The various medicaments and methods for applying the medicament to thetissue may be used sequentially in any combination or sequence inconjunction with application of the ultrasound energy (delivered withand/or without the spray, or sequentially with and without the spray inany sequence). The sequence may include wait periods during which theultrasound energy is not applied. Specifically, a treatment may includea series of treatments, wherein individual treatments of the series oftreatments are selected from the group consisting of: the treatmentincluding the steps of delivering ultrasonic energy from a non-contactdistance to the tissue simultaneous with delivery of a spray to thetissue, wherein the ultrasonic energy has an intensity capable ofpenetrating the tissue to a beneficial depth to provide a therapeuticeffect to the tissue and sonicating the spray for causing the medicamentto penetrate the tissue to a beneficial depth to provide a therapeuticeffect to the tissue; the treatment including the steps of deliveringultrasonic energy from a non-contact distance to the tissue through asubstantial expanse of a substantially purely gaseous medium to thetissue, wherein the ultrasonic energy has an intensity capable ofpenetrating the tissue to a beneficial depth to provide a therapeuticeffect to the tissue; and the treatment including the steps of themethod of the invention, wherein a different medicament is applied.

Delivery of the ultrasound energy to the medicament and to the tissueenergizes the medicament via sonication and causes penetration of themedicament into the tissue for providing an enhanced therapeutic effectto the tissue. Further, the delivery of the ultrasound energy causesexertion of acoustic pressure. The sonicated medicament and thecombination of the sonicated medicament and the low frequency ultrasoundwaves each provide at least advantages similar to the advantagesprovided by the sonicated spray and the combination of the sonicatedspray and low frequency ultrasound waves. Such advantages includeincreasing potency of the medicament, obtaining more immediate results,decreasing the volume of the medicament used relative to a volume usedfor a comparable treatment using traditional methods for achieving thesame effect, increased precision of dosage of the medicament,re-establishment of traditional antibiotics to which bacteria havebecome resistant and deeper penetration into the tissue.

The substance may be applied to surfaces other than tissue fornon-medical applications, such as cleansing, sterilizing and coatingsurfaces of objects and food.

The preceding specific embodiments are illustrative of the practice ofthe invention. It is to be understood, however, that other expedientsknown to those skilled in the art or disclosed herein, may be employedwithout departing from the spirit of the invention or the scope of theappended claims.

1-47. (canceled)
 48. An apparatus for treating a wound comprising: meansfor generating ultrasonic energy; and means for delivering the generatedultrasonic energy to the wound through a gaseous medium from anon-contact distance from the surface of the wound in the absence of acoupling medium and without direct contact between the means fordelivering the generated ultrasonic energy and the wound and otherpatient tissue, wherein the generated ultrasonic energy has an intensityin the range of about 0.25 watts/cm²-3 watts/cm², and wherein thenon-contact distance is at least 2.5 millimeters (mm) from the surfaceof the wound.
 49. The apparatus according to claim 48, wherein the meansfor generating includes means for generating the ultrasonic energy witha particular amplitude indicative of an intensity capable of achieving atherapeutic effect.
 50. The apparatus according to claim 49, wherein themeans for generating further includes the means for generating theultrasonic energy with a frequency capable of achieving the particularamplitude.
 51. The apparatus according to claim 49, wherein theparticular amplitude is at least 10 microns.
 52. The apparatus accordingto claim 49, wherein the frequency is in the range of 20 kHz-5 MHz. 53.The apparatus according to claim 50, wherein the frequency is in therange of 20-200 kHz.
 54. The apparatus according to claim 50, whereinthe frequency is in the range of 20-40 kHz.
 55. The apparatus accordingto claim 48, wherein the means for delivering includes a radiationsurface having a surface area dimensioned for achieving delivery of theultrasonic energy to the wound with an intensity capable of achieving atherapeutic effect.
 56. The apparatus according to claim 48, wherein themeans for delivering includes a radiation surface having a roundedperimeter for achieving delivery of the ultrasonic energy to the woundwith an intensity capable of achieving a therapeutic effect.
 57. Theapparatus according to claim 48, wherein the means for deliveringincludes a radiation surface; and a selection is made of at least one ofa size of a surface area of the radiation surface, a shape of aperipheral boundary of the radiation surface, a frequency of thegenerated ultrasonic energy, and an amplitude of the generatedultrasonic energy for achieving delivery of ultrasonic energy to thewound with an intensity capable of achieving a therapeutic effect. 58.The apparatus according to claim 48, wherein the means for deliveringincludes a radiation surface; and a selection is made of a combinationof a size of a surface area of the radiation surface, a shape of aperipheral boundary of the radiation surface, a shape of the curvatureof the radiation surface selected from one of flat, concave, convex anda combination thereof, a frequency of the generated ultrasonic energy,and an amplitude of the generated ultrasonic energy for achievingdelivery of ultrasonic energy to the wound with an intensity capable ofachieving a therapeutic effect.
 59. The apparatus according to claim 55,wherein a radiation surface of the means for delivering is positionedfrom 2.5 mm to 51 cm from the surface of the wound.
 60. The apparatusaccording to claim 48, wherein the means for delivering is driven by aconstant or modulated frequency having a wave form selected from thegroup consisting of sinusoidal, rectangular, trapezoidal and triangularwave forms.
 61. The apparatus according to claim 48, wherein the methodprovides a therapeutic effect selected from the group consisting ofincreasing blood flow to the wound and stimulating cell growth.
 62. Anapparatus for treating a wound comprising: an ultrasound generator; anultrasound transducer including a distal tip, which distal tip has aradiation surface from which ultrasonic energy is emitted for deliveringthe generated ultrasonic energy to the wound through a gaseous mediumfrom a non-contact distance of at least 2.5 millimeters (mm) from thesurface of the wound in the absence of a coupling medium and withoutdirect contact between the ultrasound transducer and the wound and otherpatient tissue; and a nozzle, wherein the ultrasound transducer isinterconnected to the ultrasound generator, and wherein the nozzle isattached to a portion of the ultrasound transducer to shield the distaltip.
 63. The apparatus of claim 62, wherein the ultrasonic energy has anintensity in the range of about 0.25 watts/cm²-3 watts/cm².
 64. Anapparatus for treating a wound comprising: means for generatingultrasonic energy; and means for delivering the generated ultrasonicenergy to the wound through a liquid coupling medium from a non-contactdistance from the surface of the wound without direct contact betweenthe means for delivering the generated ultrasonic energy and the woundand other patient tissue, wherein the generated ultrasonic energy has anintensity in the range of about 0.25 watts/cm²-3 watts/cm², and whereinthe non-contact distance is at least 2.5 millimeters (mm) from thesurface of the wound.
 65. The method of claim 64, wherein the liquidcoupling medium does not include a medicament.
 66. The method accordingto claim 64, wherein the liquid coupling medium is a medicament selectedfrom at least one member of the group consisting of: an antibiotic, anointment, cream, gel, liquid, salve, oil, powder, antibacterial agent,antiseptic agent, insulin, analgesic agent, conditioner, surfactant,emollient, or other active ingredients.
 67. The method according toclaim 66, wherein means for delivering the generated ultrasonic energyto the wound delivers the medicament to the wound such that themedicament penetrates the wound to a beneficial depth to provide atherapeutic effect to the wound.